The Long Noncoding RNA Lnc-EGFR Stimulates T-regulatory Cells Differentiation Thus Promoting Hepatocellular Carcinoma Immune Evasion

Overview

Journal Nat Commun

Specialty Biology

Date 2017 May 26

PMID 28541302

Citations 197

Authors

Runqiu Jiang

Junwei Tang

Yun Chen

Lei Deng

Jie Ji

Yu Xie

Ke Wang

Wei Jia

Wen-Ming Chu

Beicheng Sun

Affiliations

Soon will be listed here.

Abstract

Long noncoding RNAs play a pivotal role in T-helper cell development but little is known about their roles in Treg differentiation and functions during the progression of hepatocellular carcinoma (HCC). Here, we show that lnc-epidermal growth factor receptor (EGFR) upregulation in Tregs correlates positively with the tumour size and expression of EGFR/Foxp3, but negatively with IFN-γ expression in patients and xenografted mouse models. Lnc-EGFR stimulates Treg differentiation, suppresses CTL activity and promotes HCC growth in an EGFR-dependent manner. Mechanistically, lnc-EGFR specifically binds to EGFR and blocks its interaction with and ubiquitination by c-CBL, stabilizing it and augmenting activation of itself and its downstream AP-1/NF-AT1 axis, which in turn elicits EGFR expression. Lnc-EGFR links an immunosuppressive state to cancer by promoting Treg cell differentiation, thus offering a potential therapeutic target for HCC.

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